Structure and function of membrane transporters (Edward Yu)

We currently focus on the structural basis of multi-drug resistance
in multi-drug membrane transporters. Multi-drug transporters
interfere significantly with cancer chemotherapy and the treatment
of bacterial infections, by recognizing a number of structurally
unrelated toxic compounds and actively extruding them from cells.
Our long-term goal is to elucidate the structures and fundamental
mechanisms that give rise to multiple drug recognition and
extrusion in these multi-drug transporters. Using X-ray
crystallography and site-directed mutagenesis, we study the
structural and functional relationship of the Escherichia oli AcrB
transmembrane efflux pump, which shows the widest substrate
specificity among all known multi-drug transporters, ranging from
most of the currently used antibiotics, disinfectants, dyes,
detergents, to simple solvents. This information is expected to
help in the redesign of old drugs and the development of new drugs
as well as combinations of two or more drugs for greater effect.